SSPB_STAAU
ID SSPB_STAAU Reviewed; 393 AA.
AC P0C1S6; Q70UQ8; Q70UQ9; Q9EYW7;
DT 22-AUG-2006, integrated into UniProtKB/Swiss-Prot.
DT 22-AUG-2006, sequence version 1.
DT 03-AUG-2022, entry version 69.
DE RecName: Full=Staphopain B;
DE EC=3.4.22.-;
DE AltName: Full=Staphylococcal cysteine proteinase B;
DE AltName: Full=Staphylopain B;
DE Flags: Precursor;
GN Name=sspB;
OS Staphylococcus aureus.
OC Bacteria; Firmicutes; Bacilli; Bacillales; Staphylococcaceae;
OC Staphylococcus.
OX NCBI_TaxID=1280;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 27733 / V8, and MSSA150;
RX PubMed=15576326; DOI=10.1515/bc.2004.137;
RA Golonka E., Filipek R., Sabat A., Sinczak A., Potempa J.;
RT "Genetic characterization of staphopain genes in Staphylococcus aureus.";
RL Biol. Chem. 385:1059-1067(2004).
RN [2]
RP INTERACTION WITH STAPHOSTATIN B.
RC STRAIN=ATCC 27733 / V8;
RX PubMed=12890028; DOI=10.1046/j.1365-2958.2003.03613.x;
RA Rzychon M., Sabat A., Kosowska K., Potempa J., Dubin A.;
RT "Staphostatins: an expanding new group of proteinase inhibitors with a
RT unique specificity for the regulation of staphopains, Staphylococcus spp.
RT cysteine proteinases.";
RL Mol. Microbiol. 49:1051-1066(2003).
RN [3]
RP FUNCTION, AND MUTAGENESIS OF CYS-243.
RX PubMed=20375568; DOI=10.1159/000181014;
RA Smagur J., Guzik K., Magiera L., Bzowska M., Gruca M., Thoegersen I.B.,
RA Enghild J.J., Potempa J.;
RT "A new pathway of staphylococcal pathogenesis: apoptosis-like death induced
RT by Staphopain B in human neutrophils and monocytes.";
RL J. Innate Immun. 1:98-108(2009).
RN [4]
RP FUNCTION.
RX PubMed=19284294; DOI=10.1515/bc.2009.042;
RA Smagur J., Guzik K., Bzowska M., Kuzak M., Zarebski M., Kantyka T.,
RA Walski M., Gajkowska B., Potempa J.;
RT "Staphylococcal cysteine protease staphopain B (SspB) induces rapid
RT engulfment of human neutrophils and monocytes by macrophages.";
RL Biol. Chem. 390:361-371(2009).
RN [5]
RP FUNCTION.
RX PubMed=28438975; DOI=10.1128/iai.00177-17;
RA Elmwall J., Kwiecinski J., Na M., Ali A.A., Osla V., Shaw L.N., Wang W.,
RA Saevman K., Josefsson E., Bylund J., Jin T., Welin A., Karlsson A.;
RT "Galectin-3 Is a Target for Proteases Involved in the Virulence of
RT Staphylococcus aureus.";
RL Infect. Immun. 85:0-0(2017).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 220-393 IN COMPLEX WITH
RP STAPHOSTATIN B.
RX PubMed=12874290; DOI=10.1074/jbc.m302926200;
RA Filipek R., Rzychon M., Oleksy A., Gruca M., Dubin A., Potempa J.,
RA Bochtler M.;
RT "The staphostatin-staphopain complex: a forward binding inhibitor in
RT complex with its target cysteine protease.";
RL J. Biol. Chem. 278:40959-40966(2003).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 37-393.
RX PubMed=15518582; DOI=10.1021/bi048661m;
RA Filipek R., Szczepanowski R., Sabat A., Potempa J., Bochtler M.;
RT "Prostaphopain B structure: a comparison of proregion-mediated and
RT staphostatin-mediated protease inhibition.";
RL Biochemistry 43:14306-14315(2004).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.93 ANGSTROMS), AND ACTIVE SITE.
RX PubMed=15644332; DOI=10.1074/jbc.m411792200;
RA Filipek R., Potempa J., Bochtler M.;
RT "A comparison of staphostatin B with standard mechanism serine protease
RT inhibitors.";
RL J. Biol. Chem. 280:14669-14674(2005).
CC -!- FUNCTION: Cysteine protease that plays an important role in the
CC inhibition of host innate immune response. Degrades host elastin,
CC fibrogen, fibronectin and kininogen. Blocks phagocytosis of opsonised
CC S. aureus by neutrophils and monocytes by inducing their death in a
CC proteolytic activity-dependent manner (PubMed:20375568,
CC PubMed:19284294). Decreases surface expression of the 'don't eat me'
CC signal CD31 on neutrophils (PubMed:19284294). Cleaves host galectin-
CC 3/LGALS3, thereby inhibiting the neutrophil-activating ability of the
CC lectin (PubMed:28438975). {ECO:0000269|PubMed:19284294,
CC ECO:0000269|PubMed:20375568, ECO:0000269|PubMed:28438975}.
CC -!- ACTIVITY REGULATION: Prematurely activated/folded staphopain B is
CC inhibited by staphostatin B (SspC), which is probably required to
CC protect staphylococcal cytoplasmic proteins from degradation by SspB.
CC {ECO:0000250}.
CC -!- SUBUNIT: In the cytoplasm, prematurely activated/folded SspB forms a
CC stable non-covalent complex with SspC. {ECO:0000269|PubMed:12874290}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC -!- PTM: Proteolytically cleaved by staphylococcal serine protease (SspA).
CC {ECO:0000250}.
CC -!- MISCELLANEOUS: The cascade of activation of extracellular proteases
CC proceeds from the metalloprotease aureolysin (aur), through SspA to
CC SspB. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the peptidase C47 family. {ECO:0000305}.
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DR EMBL; AJ538363; CAD61963.1; -; Genomic_DNA.
DR EMBL; AJ538364; CAD61964.1; -; Genomic_DNA.
DR RefSeq; WP_001088793.1; NZ_WKHI01000007.1.
DR PDB; 1PXV; X-ray; 1.80 A; A/B=220-393.
DR PDB; 1X9Y; X-ray; 2.50 A; A/B/C/D=37-393.
DR PDB; 1Y4H; X-ray; 1.93 A; A/B=220-393.
DR PDBsum; 1PXV; -.
DR PDBsum; 1X9Y; -.
DR PDBsum; 1Y4H; -.
DR AlphaFoldDB; P0C1S6; -.
DR SMR; P0C1S6; -.
DR MEROPS; C47.002; -.
DR BRENDA; 3.4.22.48; 3352.
DR EvolutionaryTrace; P0C1S6; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0008234; F:cysteine-type peptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR Gene3D; 3.10.500.10; -; 1.
DR InterPro; IPR046350; Cystatin_sf.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR025660; Pept_his_AS.
DR InterPro; IPR008750; Peptidase_C47.
DR InterPro; IPR028076; Staphopain_pro.
DR InterPro; IPR037155; Staphopain_pro_sf.
DR Pfam; PF05543; Peptidase_C47; 1.
DR Pfam; PF14731; Staphopain_pro; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR SUPFAM; SSF54403; SSF54403; 1.
DR PROSITE; PS00639; THIOL_PROTEASE_HIS; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Hydrolase; Protease; Secreted; Signal; Thiol protease;
KW Virulence; Zymogen.
FT SIGNAL 1..36
FT PROPEP 37..219
FT /evidence="ECO:0000250"
FT /id="PRO_0000026559"
FT CHAIN 220..393
FT /note="Staphopain B"
FT /id="PRO_0000026560"
FT ACT_SITE 243
FT /evidence="ECO:0000269|PubMed:15644332"
FT ACT_SITE 340
FT /evidence="ECO:0000269|PubMed:15644332"
FT ACT_SITE 360
FT /evidence="ECO:0000269|PubMed:15644332"
FT SITE 219..220
FT /note="Cleavage; by SspA"
FT /evidence="ECO:0000250"
FT MUTAGEN 243
FT /note="C->A: Complete loss of effect on human neutrophils
FT death."
FT /evidence="ECO:0000269|PubMed:20375568"
FT CONFLICT 5
FT /note="C -> Y (in Ref. 1; CAD61964)"
FT /evidence="ECO:0000305"
FT CONFLICT 7
FT /note="T -> S (in Ref. 1; CAD61964)"
FT /evidence="ECO:0000305"
FT CONFLICT 182..185
FT /note="ANNI -> PGNV (in Ref. 1; CAD61964)"
FT /evidence="ECO:0000305"
FT CONFLICT 196..197
FT /note="PQ -> SK (in Ref. 1; CAD61964)"
FT /evidence="ECO:0000305"
FT CONFLICT 204
FT /note="T -> N (in Ref. 1; CAD61964)"
FT /evidence="ECO:0000305"
FT CONFLICT 283
FT /note="A -> S (in Ref. 1; CAD61964)"
FT /evidence="ECO:0000305"
FT CONFLICT 310
FT /note="N -> E (in Ref. 1; CAD61964)"
FT /evidence="ECO:0000305"
FT STRAND 44..48
FT /evidence="ECO:0007829|PDB:1X9Y"
FT HELIX 54..74
FT /evidence="ECO:0007829|PDB:1X9Y"
FT STRAND 82..84
FT /evidence="ECO:0007829|PDB:1X9Y"
FT STRAND 99..107
FT /evidence="ECO:0007829|PDB:1X9Y"
FT STRAND 110..119
FT /evidence="ECO:0007829|PDB:1X9Y"
FT HELIX 122..126
FT /evidence="ECO:0007829|PDB:1X9Y"
FT TURN 129..131
FT /evidence="ECO:0007829|PDB:1X9Y"
FT STRAND 134..139
FT /evidence="ECO:0007829|PDB:1X9Y"
FT HELIX 143..148
FT /evidence="ECO:0007829|PDB:1X9Y"
FT STRAND 150..153
FT /evidence="ECO:0007829|PDB:1X9Y"
FT STRAND 155..161
FT /evidence="ECO:0007829|PDB:1X9Y"
FT STRAND 164..169
FT /evidence="ECO:0007829|PDB:1X9Y"
FT STRAND 172..178
FT /evidence="ECO:0007829|PDB:1X9Y"
FT TURN 182..186
FT /evidence="ECO:0007829|PDB:1X9Y"
FT HELIX 196..201
FT /evidence="ECO:0007829|PDB:1X9Y"
FT STRAND 204..206
FT /evidence="ECO:0007829|PDB:1X9Y"
FT STRAND 222..227
FT /evidence="ECO:0007829|PDB:1PXV"
FT STRAND 239..241
FT /evidence="ECO:0007829|PDB:1PXV"
FT HELIX 243..256
FT /evidence="ECO:0007829|PDB:1PXV"
FT HELIX 263..270
FT /evidence="ECO:0007829|PDB:1PXV"
FT TURN 276..278
FT /evidence="ECO:0007829|PDB:1PXV"
FT HELIX 279..281
FT /evidence="ECO:0007829|PDB:1PXV"
FT HELIX 286..295
FT /evidence="ECO:0007829|PDB:1PXV"
FT STRAND 301..305
FT /evidence="ECO:0007829|PDB:1PXV"
FT HELIX 309..317
FT /evidence="ECO:0007829|PDB:1PXV"
FT STRAND 322..327
FT /evidence="ECO:0007829|PDB:1PXV"
FT STRAND 333..335
FT /evidence="ECO:0007829|PDB:1X9Y"
FT STRAND 339..350
FT /evidence="ECO:0007829|PDB:1PXV"
FT STRAND 353..359
FT /evidence="ECO:0007829|PDB:1PXV"
FT STRAND 367..370
FT /evidence="ECO:0007829|PDB:1PXV"
FT STRAND 375..378
FT /evidence="ECO:0007829|PDB:1PXV"
FT HELIX 379..381
FT /evidence="ECO:0007829|PDB:1PXV"
FT STRAND 382..391
FT /evidence="ECO:0007829|PDB:1PXV"
SQ SEQUENCE 393 AA; 44576 MW; 0FED1862C0408123 CRC64;
MNSSCKTRVF NIISIIMVSM LILSLGAFAN NNKAKADSHS KQLEINVKSD KVPQKVKDLA
QQQFAGYAKA LDKQSNAKTG KYELGEAFKI YKFNGEEDNS YYYPVIKDGK IVYTLTLSPK
NKDDLNKSKE DMNYSVKISN FIAKDLDQIK DKNSNITVLT DEKGFYFEED GKVRLVKATP
LANNIKEKES AKTVSPQLKQ ELKTTVTPTK VEENEAIQED QVQYENTLKN FKIREQQFDN
SWCAGFSMAA LLNATKNTDT YNAHDIMRTL YPEVSEQDLP NCATFPNQMI EYGKSQGRDI
HYQEGVPSYN QVDQLTKDNV GIMILAQSVS QNPNDPHLGH ALAVVGNAKI NDQEKLIYWN
PWDTELSIQD ADSSLLHLSF NRDYNWYGSM IGY
